Pharmacogenomics is the research field that aims to understand how variations in the human genome affect responses to medication. PD patients exhibit conspicuous (but unexplained) differences in treatment response (drug efficacy) and susceptibility to develop side effects (e.g. motor complications, impulsive-compulsive disorders) when chronically exposed to dopaminergic medication. This heterogeneity may depend upon individual differences in the complex interplay between genetic determinants underpinning the disease, pharmacokinetics (including drug absorption, distribution, metabolism and elimination), as well as drug target effects. Obviously, this phenomenon is not restricted to the dopamine system, but also involves treatments targeting other neurotransmitter systems affected in PD (e.g. serotonergic, glutamatergic).
Further, polypharmacy involving antiparkinson drugs and drugs used for co-morbidity is common in patients with PD. This renders patients at risk for consequences of altered drug metabolism; e.g. loss of efficacy or occurrence of toxic side-effects.
Against this background, we are currently developing a research program that aims to study how genetic variants may affect the efficacy and tolerability of drugs prescribed for patients with PD. If successful, actionable drug prescribing could be used to tailor drug selection to the characteristics of the individual patient (‘personalised therapeutics’). The identification of genes that are associated with differences in response to medication may increase our understanding of the pathways involved and may ultimately contribute to the development of new medication.